Kombe Kombe Arnaud John, Zahid Ayesha, Mohammed Ahmed, Shi Ronghua, Jin Tengchuan
Department of Obstetrics and Gynecology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Hefei National Laboratory for Physical Sciences at Microscale, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Front Mol Biosci. 2021 May 31;8:670815. doi: 10.3389/fmolb.2021.670815. eCollection 2021.
The 2019-2020 winter was marked by the emergence of a new coronavirus (SARS-CoV-2) related disease (COVID-19), which started in Wuhan, China. Its high human-to-human transmission ability led to a worldwide spread within few weeks and has caused substantial human loss. Mechanical antiviral control approach, drug repositioning, and use of COVID-19 convalescent plasmas (CPs) were the first line strategies utilized to mitigate the viral spread, yet insufficient. The urgent need to contain this deadly pandemic has led searchers and pharmaceutical companies to develop vaccines. However, not all vaccines manufactured are safe. Besides, an alternative and effective treatment option for such an infectious disease would include pure anti-viral neutralizing monoclonal antibodies (NmAbs), which can block the virus at specific molecular targets from entering cells by inhibiting virus-cell structural complex formation, with more safety and efficiency than the CP. Indeed, there is a lot of molecular evidence about the protector effect and the use of molecular feature-based NmAbs as promising therapeutics to contain COVID-19. Thus, from the scientific publication database screening, we here retrieved antibody-related papers and summarized the repertory of characterized NmAbs against SARS-CoV-2, their molecular neutralization mechanisms, and their immunotherapeutic pros and cons. About 500 anti-SARS-CoV-2 NmAbs, characterized through competitive binding assays and neutralization efficacy, were reported at the writing time (January 2021). All NmAbs bind respectively to SARS-CoV-2 S and exhibit high molecular neutralizing effects against wild-type and/or pseudotyped virus. Overall, we defined six NmAb groups blocking SARS-CoV-2 through different molecular neutralization mechanisms, from which five potential neutralization sites on SARS-CoV-2 S protein are described. Therefore, more efforts are needed to develop NmAbs-based cocktails to mitigate COVID-19.
2019 - 2020年冬季，一种新型冠状病毒（SARS-CoV-2）相关疾病（COVID-19）出现，该疾病始于中国武汉。其高人际传播能力导致在几周内全球蔓延，并造成了大量人员伤亡。机械抗病毒控制方法、药物重新定位以及使用COVID-19康复期血浆（CP）是最初用于减轻病毒传播的一线策略，但并不充分。遏制这一致命大流行的迫切需求促使研究人员和制药公司研发疫苗。然而，并非所有生产的疫苗都是安全的。此外，针对这种传染病的另一种有效治疗选择包括纯抗病毒中和单克隆抗体（NmAb），它可以通过抑制病毒 - 细胞结构复合物的形成，在特定分子靶点阻断病毒进入细胞，比CP更安全、高效。事实上，有很多分子证据表明基于分子特征的NmAb具有保护作用，有望作为治疗COVID-19的药物。因此，通过科学出版物数据库筛选，我们在此检索了抗体相关论文，并总结了已鉴定的针对SARS-CoV-2的NmAb库、它们的分子中和机制以及免疫治疗的优缺点。在撰写本文时（2021年1月），通过竞争结合试验和中和效力鉴定的约500种抗SARS-CoV-2 NmAb已被报道。所有NmAb分别与SARS-CoV-2 S结合，并对野生型和/或假型病毒表现出高分子中和作用。总体而言，我们定义了六个通过不同分子中和机制阻断SARS-CoV-2的NmAb组，其中描述了SARS-CoV-2 S蛋白上的五个潜在中和位点。因此，需要做出更多努力来开发基于NmAb的鸡尾酒疗法以减轻COVID-19。
